How to find a mutation behind an inherited disease.

: The search for the mutations causing human diseases is reaching new gene areas with increasing speed with new cloned genes or polymorphic gene areas, being reported every week. The almost 300 cloned genes and over 1000 RFLP-loci of the human genome can be used as tools to approach most human gene defects. Once the linkage between the disease and the RFLP has been found, chromosomal "jumping" or pulsed field electrophoresis can be used to separate the DNA areas in the neighbourhood of the first found RFLP locus for more detailed studies and finally for the location of the defective gene. Once found, the detailed analysis of gene mutations still requires the use of several, technically very demanding approaches of molecular biology. New techniques, such as the multiplication of the required gene area in a test tube as well as RNase protection assays have been used successfully to pick out about 80-90% of the mutations which occur in one gene area and cause the disease of this gene area. The increased specificity and sensitivity of these modern approaches do not, however, necessarily lead to the rapid diagnosis of all inherited diseases. Even once a linkage has been established between RFLP locus and a disease the path is still a long one: as demonstrated in Duchenne's muscular dystrophy and Huntington's disease, we have diagnostic RFLP-linkages but the search for the gene defect continues. Further, the increased sensitivity of the mutation assays will eventually reveal all the variations in an individual.(ABSTRACT TRUNCATED AT 250 WORDS)